Mechanisms of Desensitization During Peanut Oral Immunotherapy (PnOIT4)

The purpose of this study is to attempt to understand how desensitization works in peanut allergic children who are undergoing oral immunotherapy (OIT) to peanut. We want to identify the early changes in the desensitization process the immune cells undergo to become desensitized to the peanut protein.

Study Overview

• Status: Completed
• Conditions: Food Hypersensitivity
• Intervention / Treatment: Drug: Open label peanut OIT

Detailed Description

Peanut allergic children will undergo an oral food challenge (OFC) to 1 gm peanut protein in order to accomplish two objectives: (1)to confirm the diagnosis of peanut allergy, and (2) to measure the amount of peanut protein it takes to cause an allergic reaction. Each subject will then undergo a modified rush phase in which the subject receives 6 doses of peanut protein in one day. The build-up phase begins afterward in which the subject's dose of peanut protein is increased every 2 weeks for 36 weeks. After the final build-up dose, the subject consumes that dose for 2 weeks after which he or she returns to the food allergy center for the second food challenge. If the subject successfully consumes this food challenge without symptoms, the daily dosing of peanut protein will be stopped and the subject will then undergo a third food challenge. If the subject successfully consumes the peanut protein during that challenge, he or she will return for a fourth food challenge to peanut.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 4 to up to 12 years of age of any gender, race, or ethnicity.
• Minimum weight 16 kg at the time of enrollment.
• Physician diagnosis of peanut allergy OR convincing clinical history of an allergic reaction to peanut.
• Detectable serum peanut -specific IgE level (CAP-FEIA ≥ 0.35 kU/L) and a positive SPT (wheal ≥ 3mm on skin prick test to peanut extract compared to a negative control.)
• Allergic reaction to ≤ 1 gm peanut protein during a blinded oral challenge test conducted at screening (e.g., a double-blinded, placebo-controlled food challenge [DBPCFC]).
• Written informed consent from parent/guardian.
• Written assent from subject if applicable
• Consumption of oat-containing product within 90 days prior to enrollment

Exclusion Criteria:

• History of allergic reaction to peanut consistent with severe anaphylaxis (defined as hypotension/shock; or neurologic impairment).
• Chronic disease other than asthma, atopic dermatitis, rhinitis requiring therapy; e.g., heart disease or diabetes.
• Active eosinophilic gastrointestinal disease in the past 2 years
• Participation in any interventional study for the treatment of food allergy in the 6 months prior to visit -1
• Inhalant allergen immunotherapy that has not yet reached maintenance dosing.
• Asthma defined as moderate or severe persistent by National Asthma Education and Prevention Program Expert Panel Guidelines (e.g. asthma that requires more than fluticasone 440 mcg or its equivalent daily for adequate control).
• Inability to discontinue antihistamines for skin testing, OFC and the initial dose escalation.
• Use of omalizumab or other non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) in the 12 months prior to visit -1.
• Any systemic therapy which in the judgment of the investigator could be immunomodulatory (e.g. rituximab) in the 12 months prior to visit -1, Systemic corticosteroid therapy of up to a total of three weeks is allowed.
• Use of investigational drug in 90 days prior to visit -1.
• Plan to use any investigational drug during the study period.
• The presence of any medical condition that the investigator deems incompatible with participation in the trial.
• Inability to speak English.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open label peanut OIT; Open label orally ingested peanut flour with maintenance dose of 1450mg	Drug: Open label peanut OIT; Subject will take increasing amounts of peanut protein up to a maximum maintenace dose of 1450mg.; Other Names: Peanut flour

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Who Develop Desensitization	The percentage of peanut allergic subjects who develop desensitization as defined by being able to consume 5000mg of peanut protein during a double blind food challenge after completing a build-up phase of peanut OIT.	40 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Who Maintain Desensitization Once OIT is Stopped	The percentage of subjects who maintain desensitization once the OIT is withdrawn at 1, 2, 3, and 4 week intervals.	4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Wheal Diameter, as Assessed by the Skin Prick Test (SPT) to Peanut	Allergic reactivity of mast cells is assessed by skin prick testing through measurement of the wheal diameter after exposure to peanut. This outcome measure reports the change in skin prick test wheal diameter from baseline through the end of the treatment period.	44 weeks
Change in Peanut Specific Immunoglobin E (IgE) From Baseline Until Desensitization Food Challenge	The investigation of mechanistic changes that occur in the immune system over the duration of the study - Peanut specific immunoglobin E (IgE)	44 weeks
Change in Immunoglobin G4 (IgG4) to Peanut From Baseline Until Desensitization Food Challenge	The investigation of mechanistic changes that occur in the immune system dover the duration of the study - Immunoglobin G4 (IgG4) to peanut	44 weeks

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Wesley Burks, MD, UNC Chapel Hill; Principal Investigator: Edwin Kim, MD, UNC Chapel Hill

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: March 15, 2013
• First Submitted That Met QC Criteria: March 15, 2013
• First Posted (Estimate): March 19, 2013

Study Record Updates

• Last Update Posted (Actual): March 1, 2018
• Last Update Submitted That Met QC Criteria: February 27, 2018
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Peanut allergy
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Food Hypersensitivity
• Other Study ID Numbers: 13-0900; R01AI068074 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO